The goal of this project is to understand aspects of the pathogenesis of herpes simplex virus (HSV) infection in the nervous system including the mechanism by which this neurotropic virus is regulated within neuronal and nonneuronal cells during acute and long term infections. A further objective is to understand the relationship between HSV infection and disease. During FY 95 studies were initiated to examine whether the HSV- 1 major immediate early gene (ICP4) is transcriptionally active in latently infected ganglia. Transgenic mice containing the HSV-1 ICP4 promoter sequence fused to the E. coli beta galactosidase coding sequence were analyzed after infection with HSV-1. Nonneuronal cells morphologically identified as Schwann cells were positive for beta- galactosidase in latently infected trigeminal ganglia. Neurons were negative for ICP4 promoter activity in latently infected ganglia. This suggests that chronic infections of nonneuronal cells of ganglia are regulated by a different mechanism than latently infected neurons. The viral gene expression in nonneuronal cells of ganglia may be the underlying cause for chronic inflammatory lesions in HSV-1 infected trigeminal ganglia of mice. It is also possible that this mechanism could function in chronic inflammatory diseases of sensory ganglia of humans.